Abstract 812MO
Background
PAOLA-1/ENGOT-ov25 (NCT02477644) is a phase III trial in pts with newly diagnosed, FIGO stage III‒IV HGOC. Adding olaparib to maintenance bev after first-line platinum-based chemotherapy + bev led to a statistically significant progression-free survival (PFS) benefit in pts with advanced HGOC (hazard ratio 0.59; 95% confidence interval 0.49–0.72; P<0.001) (Ray-Coquard et al. NEJM 2019). Recently, the FDA approved olaparib + bev maintenance following first-line platinum-based chemotherapy response in homologous recombination deficiency (HRD) positive pts. We explored ORR for pts with residual disease in PAOLA-1.
Methods
Pts with no evidence of disease or clinical complete response (CR) or partial response (PR) after platinum-based chemotherapy + bev received olaparib tablets (300 mg bid for up to 24 months) + bev (15 mg/kg q3w for 15 months in total) or placebo + bev. In pts with evidence of disease (target and/or non-target lesions) and/or cancer antigen-125 (CA-125) ≥2 x upper limit at baseline (assessment following initial therapy), we explored ORR according to GCIG criteria (Rustin at al. IJGC 2011).
Results
Of 806 randomised pts, 216 (27%) had evidence of disease and/or CA-125 ≥2 x upper limit at baseline (Table). RECIST and/or CA-125 ORR was improved with olaparib + bev vs placebo + bev, with the greatest benefit seen in BRCAm pts and in HRD-positive pts (Table). Table: 812MO
| N (%) | BRCAm population | HRD-positive population | ITT population | |||
| O + B (n=157) | P + B (n=80) | O + B (n=255) | P + B (n=132) | O + B (n=537) | P + B (n=269) | |
| Evidence of disease (target/non-target lesions) at baseline | 28 (18) | 19 (24) | 49 (19) | 32 (24) | 129 (24) | 73 (27) |
| Best overall RECIST response CR PR SD | 16 (57) 2 (7) 7 (25) | 5 (26) 3 (16) 9 (47) | 21 (43) 5 (10) 20 (41) | 7 (22) 3 (9) 18 (56) | 32 (25) 7 (5) 61 (47) | 13 (18) 5 (7) 40 (55) |
| RECIST ORR | 18 (64) | 8 (42) | 26 (53) | 10 (31) | 39 (30) | 18 (25) |
| Elevated CA-125 at baseline* | 6 (4) | 5 (6) | 10 (4) | 8 (6) | 28 (5) | 17 (6) |
| CA-125 ORR | 5 (83) | 3 (60) | 7 (70) | 5 (63) | 10 (36) | 5 (29) |
| Total evaluable population | 29 (18) | 20 (25) | 51 (20) | 35 (27) | 138 (26) | 78 (29) |
| ORR according to RECIST and/or CA-125 | 23 (79) | 10 (50) | 32 (63) | 14 (40) | 48 (35) | 22 (28) |
*At least twice upper limit; B, bevacizumab; ITT, intent to treat; O, olaparib; PD, progressive disease; SD, stable disease.
Conclusions
In PAOLA-1, maintenance bev alone achieves a substantial ORR in pts with residual disease after initial therapy. Adding olaparib improved ORRs compared with bev. In both maintenance arms, BRCAm and HRD-positive pts are deriving the greatest benefit.
Clinical trial identification
NCT02477644.
Editorial acknowledgement
Medical writing support was provided by Catherine Risebro, PhD, and Claire Routley, PhD, of Mudskipper Business Limited.
Legal entity responsible for the study
ARCAGY Research.
Funding
ARCAGY Research, AstraZeneca, Merck & Co., and F. Hoffmann-La Roche.
Disclosure
N. Colombo: Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Tesaro; Advisory/Consultancy: BioCad; Advisory/Consultancy: GSK. J. Gantzer: Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Chugai. B. Ataseven: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Honoraria (self): Celgene; Honoraria (self): Clovis Oncology; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: PharmaMar. G. Scambia: Speaker Bureau/Expert testimony: Clovis Oncology Italy S.r.l; Speaker Bureau/Expert testimony: MSD Italia S.r.l. A. Herrero: Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK/Tesaro. P. Sevelda: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Roche. P. Vuylsteke: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: PharmaMar. P. Buderath: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: Tesaro; Travel/Accommodation/Expenses: PharmaMar. C. Pisano: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK/Tesaro. A. El-Balat: Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Olympus; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Teva. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sereno; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche/Genentech; Non-remunerated activity/ies: GINECO; Non-remunerated activity/ies: ENGOT; Non-remunerated activity/ies: GCIG; Non-remunerated activity/ies: European Community; Non-remunerated activity/ies: ESMO; Non-remunerated activity/ies: ASCO; Non-remunerated activity/ies: ESGO; Non-remunerated activity/ies: IGSC; Non-remunerated activity/ies: Inca. Swiss; Non-remunerated activity/ies: Italian, Belgium and German health authorities. All other authors have declared no conflicts of interest.